Copper-Catalyzed Intramolecular C(sp3)-H and C(sp2)-H Amidation by Oxidative Cyclization

The first copper-catalyzed intramolecular C(sp(3))H and C(sp(2))H oxidative amidation has been developed. Using a Cu(OAc)(2) catalyst and an Ag2CO3 oxidant in dichloroethane solvent, C(sp(3))H amidation proceeded at a terminal methyl group, as well as at the internal benzylic position of an alkyl chain. This reaction has a broad substrate scope, and various -lactams were obtained in excellent yield, even on gram scale. Use of CuCl2 and Ag2CO3 under an O-2 atmosphere in dimethyl sulfoxide, however, leads to 2-indolinone selectively by C(sp(2))H amidation. Kinetic isotope effect (KIE) studies indicated that CH bond activation is the rate-determining step. The 5-methoxyquinolyl directing group could be removed by oxidation.